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Triphenylphosphite neuropathy in hens
F Fioroni1, A Moretto, M Lotti
1Istituto di Medicina del Lavoro, Università degli Studi di Padova, Italy.
Archives of Toxicology
|January 1, 1995
Summary
Triphenyl phosphite (TPP) causes neurotoxicity in hens, similar to organophosphate-induced delayed polyneuropathy (OPIDP). Phenylmethanesulfonyl fluoride (PMSF) exhibits dual effects, protecting against or exacerbating TPP neuropathy depending on timing, suggesting OPIDP is the primary mechanism.
Area of Science:
- Neurotoxicology
- Toxicology
- Pharmacology
Background:
- Triphenyl phosphite (TPP), a trivalent phosphorus compound, induces ataxia and paralysis in hens.
- TPP-induced neurotoxicity exhibits distinct characteristics from organophosphate-induced delayed polyneuropathy (OPIDP), a condition caused by pentavalent phosphorus compounds.
- Phenylmethanesulfonyl fluoride (PMSF) has shown differential effects, partially protecting against or exacerbating TPP neurotoxicity based on dosage.
Purpose of the Study:
- To investigate the neurotoxic mechanisms of TPP in hens, focusing on its relationship with OPIDP.
- To explore the dual role of PMSF (protection and promotion) in TPP-induced neuropathy.
- To elucidate the underlying reasons for the observed differences and similarities between TPP and OPIDP.
Main Methods:
- Administered single doses of TPP to hens to induce neurotoxicity.
- Investigated the effects of PMSF pretreatment and post-treatment on TPP-induced neuropathy.
- Monitored clinical signs, neuropathy target esterase (NTE) inhibition and reappearance, and axonal transport.
- Analyzed the time course of NTE inhibition and reappearance after TPP and PMSF administration.
Main Results:
- TPP neuropathy in hens shares clinical signs with OPIDP, appearing 7-12 days post-treatment.
- TPP treatment led to significant NTE inhibition (>70%) and aging, with a longer NTE reappearance half-life compared to PMSF.
- PMSF demonstrated dose-dependent effects, partially protecting when given before TPP and promoting neuropathy when given afterwards, up to 12 days post-TPP.
Conclusions:
- TPP-induced neuropathy in hens is likely identical to typical OPIDP, primarily mediated by NTE inhibition.
- The complex interactions between TPP and PMSF are explained by TPP's prolonged pharmacokinetics and PMSF's dual action on NTE and a separate promotion site.
- The observed differences in onset and PMSF effects are attributed to TPP's slow kinetics and dose-dependent interactions with NTE.